Introduction

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare, accounting for <1% of ampullary neoplasms. Their presentation is often nonspecific, and cross-sectional imaging may miss small or infiltrative lesions, especially when they grow submucosally. Endoscopy plays a critical role when symptoms persist despite unrevealing imaging.

Case Report

A 47-year-old woman with a history of cholangiopancreatitis presented with recurrent abdominal pain, nausea, and progressive constitutional symptoms. Previous imaging had shown biliary and pancreatic duct dilation without an identifiable cause. A repeat MRCP demonstrated ampullary obstruction but no mass. ERCP revealed a markedly abnormal papilla, characterized by friability, firmness, erythema, and an unusually en bloc mobility that prevented biliary cannulation. Biopsies were obtained and a prophylactic pancreatic stent was placed.

Histology demonstrated a well-differentiated grade 3 neuroendocrine tumor (Ki-67 25%, CK19/CK7 positive). Staging found no metastases, but surgical exploration identified multiple small liver lesions consistent with metastatic NET. Resection revealed a 3-cm ampullary NET infiltrating the pancreatic head with lymphovascular and perineural invasion, as well as regional lymph-node involvement, consistent with pT3 N1 M1 disease. A synchronous well-differentiated grade 2 pancreatic tail NET (1 cm) was also identified, suggesting multifocal disease.

Discussion

Ampullary NETs tend to behave more aggressively than other gastrointestinal or pancreatic NETs of comparable size. Reported rates of nodal involvement and liver metastases are high, even in small tumors. This case illustrates the diagnostic limitations of MRCP and CT for detecting early or infiltrative ampullary lesions and reinforces the value of endoscopy as the most sensitive tool for identifying abnormal papillary morphology. Immunohistochemistry confirms neuroendocrine differentiation, while Ki-67 remains essential for grading and prognosis. Management typically requires radical surgical resection. In advanced disease, therapeutic options include somatostatin analogues, targeted agents, peptide receptor radionuclide therapy, or systemic chemotherapy.

Conclusion

This case highlights the central diagnostic role of endoscopy in evaluating ampullary lesions that remain occult on imaging. The combination of atypical papillary features, multifocal NETs, and unexpected metastatic disease underscores the aggressive potential of ampullary NETs and the importance of maintaining clinical suspicion in patients with persistent symptoms.